Neural Characteristics in Non-Suicidal Self-Injury and its Relation to Pain: A Functional and Structural MRI Study

Abstract Importance Pain is inherently aversive but provides emotional relief for individuals engaging in non-suicidal self-injury (NSSI). Despite the high prevalence and severity of NSSI, the neural mechanisms underlying pain processing in individuals with NSSI remain poorly understood. Objective To compare brain structure and functional connectivity between individuals with NSSI and controls and to relate brain function to pain inhibition. Design Cross-sectional, experimental. Setting MR Center at the Karolinska University Hospital in Stockholm, Sweden. Participants Women aged 18-35 years with NSSI (n=41) or matched healthy controls (n=40). Exposures Engagment in self-injury ≥ 5 days during the last year. Main outcomes and measures Magnetic Resonance Imaging (MRI) was used to examine brain structure and function related to pain regulation in individuals with NSSI (n=41) and healthy controls (n=40). The experimental pain test Conditioned Pain Modulation (CPM) was used to determine descending pain inhibition. Results We found higher connectivity between the brain’s somatomotor networks and subcortical areas during resting-state functional MRI in NSSI compared to controls ( P =.009; Bonferroni corrected), particularly involving the thalamus and caudate nucleus. The connectivity was linked to the level of descending pain inhibition during CPM. There was no difference between NSSI and controls regarding brain morphometry. Conclusions and relevance Our findings suggest that individuals with NSSI may rely more on sensory-motor activations to regulate emotions. This study provides the first evidence linking specific brain circuits to pain regulation and self-injury behavior, highlighting potential pathways for more effective treatments for NSSI and related mental health conditions.